Alchemical Free Energy Perturbation Predicts Relative Binding Affinities of Propofol Analogs and Etomidate Stereoisomers at the GABAAR

This dataset contains the complete input and output files from Free Energy Perturbation (FEP) calculations performed using BIOVIA Discovery Studio. The data supports the evaluation of relative binding free energy (ΔΔG) predictions for two systems of anesthetic compounds. Dataset 1: Propofol Congeneric Series FEP calculations for 13 propofol analogs bound to the GABA_A receptor (PDB: 6X3T). Relative binding free energies were computed across 12 ligand pairs using a perturbation graph anchored to diisopropylphenol (propofol). Three independent replicate runs (Run1, Run2, Run3) were performed to assess reproducibility. - Propofol_misc.zip - Protein structure (6X3T.dsv) and ligand library (13_propofol_analogs.sd) - Propofol_Run[1-3]_Input.zip - Solvated complex/ligand systems and FEP protocol files for each replicate- Propofol_Run[1-3]_Output.zip - FEP trajectories, calculated ΔΔG values(calc_relative_ddG.csv), free energy reports, and per-lambda-window simulation data for each replicate Dataset 2: R- vs S-Etomidate Enantioselectivity FEP calculation comparing the relative binding free energy of R-etomidate and S-etomidate to evaluate stereoselective binding. - RvsS-Etomidate_Input.zip - Solvated complex/ligand systems and FEP protocol- RvsS-Etomidate_Output_and_Plots.zip - FEP output, calculated ΔΔG values, and analysis plots (free energy vs. lambda, hysteresis, summary bar charts, and CDOCKER vs. potency correlations) Software: BIOVIA Discovery Studio (FEP protocol) Keywords: Free Energy Perturbation, FEP, relative binding free energy, propofol, etomidate, GABA_A receptor, molecular dynamics, alchemical free energy, drug binding, anesthetics